Article
Chemistry, Organic
Nariyoshi Umekubo, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi
Summary: Bicyclo[2.2.2]octane derivatives with a quaternary bridgehead carbon were synthesized in nearly optically pure form with excellent diastereoselectivity using diphenylprolinol silyl ether mediated domino Michael/Michael reaction of alpha,beta-unsaturated aldehyde and cyclohex-2-en-1-one containing an electron-withdrawing group at the 3-position. Carbonitrile, alkoxycarbonyl, and sulfonyl substituents proved to be effective electron-withdrawing groups at the 3-position of cyclohex-2-en-1-one.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Applied
Yong-Xing Song, Da-Ming Du
Summary: The aza-Michael addition cascade reaction is an important synthetic method for constructing functionalized C-N bonds, widely used in the synthesis of chiral drugs, intermediates, and natural products. This review highlights recent developments in asymmetric synthesis, including various types of aza-Michael addition triggered cascade reactions, reaction mechanisms, and derivatization experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Yujiro Hayashi, Shusuke Hattori, Seitaro Koshino
Summary: Flow reactions using an immobilized diphenylprolinol alkyl ether catalyst 2 were investigated for alpha,beta-unsaturated aldehydes and nitroalkanes. The reactions showed fast reaction rates and excellent enantioselectivity with good overall yields and turnover numbers.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Organic
Amaechi Shedrack Odoh, Louise Aidanpaa, Nariyoshi Umekubo, Hiroaki Matoba, Naoki Mori, Yujiro Hayashi
Summary: The asymmetric domino Michael/Michael reaction catalyzed by diphenylprolinol silyl ether results in the formation of penta-substituted cyclohexanes with three continuous chiral centers, showing excellent diastereo- and enantioselectivity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ruiying Ma, Hongzhou Yang, Ling Ye, Qiang Yang, Zhichuan Shi, Zhigang Zhao, Xuefeng Li
Summary: A one-pot, two-step aza-Michael/Michael/Michael process has been developed for the diastereospecific construction of C6a,C10acis-hydrophenanthridines in a highly enantioselective manner (83-99% ee). The tricyclic products were obtained in 50-99% isolated yields, sequentially promoted by bifunctional squaramide and diamine in a one-pot operation. This doubly annulative protocol demonstrates the facile construction of complex polycyclic structures through the full utilization of available reaction sites in readily prepared precursors.
Article
Chemistry, Applied
Jen-Yu Kuan, I-Ting Chen, Hsuan Lin, Jeng-Liang Han
Summary: We have developed a substrate-dependent, regio- and stereocontrolled diversity-oriented organocatalytic vinylogous Michael addition/cyclization cascade of 2-alkylidene indane-1,3-diones with enals, using secondary amines as the catalyst. This method allows for the selective synthesis of spiroindane-1,3-diones, tetrahydrofluoren-9-one derivatives, and benzofused oxabicyclo[3.3.1]nonanes. Plausible catalytic pathways have been proposed, and DFT calculations have clarified the mechanisms involved.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Yu-Xia Liu, Zhi-Wei Ma, Chuan-Chuan Wang, Qian Li, Wen-Peng Mai
Summary: This study demonstrates the application of isosteviol-derived bifunctional primary amine-squaramide organocatalysts in the Michael addition reaction between nitroalkenes and acetophenone, yielding high yields and good enantioselectivity at room temperature.
LETTERS IN ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Organic
Soumik De, Aritra Kumar Dan, Raghaba Sahu, Debadutta Das
Summary: This review focuses on the role and mechanisms of various catalysts in synthesizing halocyclized products, highlighting the enantioselectivities, diastereoselectivities, and regioselectivities studied in existing literature.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Rui Yang, Zeyu Zhou, Huanfeng Jiang, Toh-Seok Kam, Kai Chen, Zhiqiang Ma
Summary: The first asymmetric total synthesis of the monoterpenoid indole alkaloid arboduridine has been achieved. The synthesis involves several reactions to construct the complex structure and demonstrates a highly enantioselective synthetic strategy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Yong Tang, Kaihong Liu, Ye Wu, Siyu Zhou, Tanyu Cheng, Guohua Liu
Summary: The development of cooperative catalysis is important for multi-step sequential enantioselective organic transformations. This study presents the design of an integrated Cu/bisoxazoline and Ru/diamine co-catalyst system for the direct preparation of 1,3-distereocentered beta-sulfonamido alcohols. The cascade reaction enables efficient and selective synthesis of chiral products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Khadijah Anwar, Francisco Jose Aguilar Troyano, Ayham H. Abazid, Oumayma El Yarroudi, Ignacio Funes-Ardoiz, Adrian Gomez-Suarez
Summary: Here, we present a highly modular strategy for synthesizing spirocyclic scaffolds from easily available starting materials, such as cyclic ketones and alpha-amino or oxamic acids. The reaction involves a simple Knoevenagel condensation, followed by a cascade Giese-type reaction and base-mediated cyclization, resulting in a wide range of polar spirocyclic products in high yields. Our method allows for easy diversification of the products, thus providing rapid access to libraries of potential drug-like molecules.
Article
Chemistry, Multidisciplinary
Ken-Loon Choo, Bijan Mirabi, Karl Z. Demmans, Mark Lautens
Summary: Enantioenriched spiro-oxiranes with three contiguous stereocenters were synthesized using a rhodium-catalyzed cascade reaction, enabling the formation of a spirocyclic framework in a single step. Both sp(2)- and sp-hybridized carbon nucleophiles were found to be efficient initiators, yielding products with different functional groups. Derivatization studies demonstrated the synthetic versatility of the products' epoxide and alkyne moieties. DFT calculations were employed to explain spectroscopic discrepancies between solution- and solid-state structures of the products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Yongkang Song, Jian Wang, Shaomin Deng, Guohua Liu, Tanyu Cheng
Summary: Domino catalytic reactions are a powerful strategy for synthesizing complex and high-value compounds. In this study, a domino enantioselective Michael addition/cyclization process, catalyzed by inexpensive and readily available quinidine, was developed. The reaction proceeded smoothly under mild conditions at room temperature within 2 hours, affording chiral 1,4-dihydro-pyridine containing benzosultams in good yields (up to 95%) and excellent enantioselectivities (up to 99% ee).
MOLECULAR CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Eleonora Grandi, Michele Crotti, Marie-Catherine Sigmund, Guangcai Xu, Pieter G. G. Tepper, Gerrit J. J. Poelarends
Summary: Multi-enzymatic cascades using engineered enzymes are a useful tool for synthesizing complex molecules from simple starting materials. In this study, we engineered the enzyme 4-oxalocrotonate tautomerase (4-OT) to have increased aldolase activity. We then used the evolved 4-OT variant in a one-pot two-step cascade to synthesize enantioenriched epoxides from biomass-derived materials with high yields and enantioselectivity. We also developed a three-step enzymatic cascade for the production of chiral aromatic triols with high enantiopurity and good isolated yields.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Lorenzo Serusi, Laura Palombi, Giovanni Pierri, Antonia Di Mola, Antonio Massa
Summary: The asymmetric synthesis of novel 3-substitued isoindolinones was achieved using the asymmetric nitro-Mannich reaction and the in situ cyclization reaction. High enantioselectivities and yields were obtained in the presence of a neutral bifunctional organocatalyst. The investigation of the reactivity of the obtained products also revealed the potential for further functionalization.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Takahito Kuribara, Masaya Nakajima, Tetsuhiro Nemoto
Article
Chemistry, Organic
Masaya Nakajima, Yusuke Kondo, Shun-ichi Nakano, Yusuke Adachi, Dongil Choi, Robert Franzen, Tetsuhiro Nemoto
TETRAHEDRON LETTERS
(2020)
Article
Chemistry, Multidisciplinary
Tsubasa Ito, Shingo Harada, Haruka Homma, Hiroki Takenaka, Shumpei Hirose, Tetsuhiro Nemoto
Summary: This study developed a new method for achieving highly enantioselective dearomatization of chemically inert arenes, leading to the synthesis of polycycles with multiple stereogenic centers. Mechanistic investigations revealed the origin of chemo- and enantioselectivity in the reaction process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Applied
Mai Yanagawa, Shingo Harada, Shumpei Hirose, Tetsuhiro Nemoto
Summary: The study developed a rhodium-catalyzed C-H functionalization reaction for synthesizing 2,3-fused indole variants using an alpha,beta-unsaturated enone as a directing group and electrophile. This annulation enabled the rapid assembly of valuable hydrocarbazolones from readily available indoles, and computational investigations were conducted to elucidate the reaction pathway and site-selectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Jun Ueda, Shingo Harada, Mayu Kobayashi, Mai Yanagawa, Tetsuhiro Nemoto
Summary: A dual catalyst system consisting of maleic acid and Schreiner's thiourea was used to successfully synthesize a spiroindolenine core, providing a new approach for synthetic strategies that were previously difficult to achieve. Computational studies revealed a unique macrocyclic transition state that lowered the activation energy of the spirocyclization reaction.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Tsubasa Ito, Hiroki Takenaka, Haruka Homma, Shingo Harada, Tetsuhiro Nemoto
Summary: An asymmetric intramolecular cyclopropanation reaction under silver catalysis has been developed, producing enantioenriched gamma-lactam fused cyclopropane commonly found in bioactive molecules and pharmaceuticals. The fused cyclopropane was efficiently converted into drug candidate molecules in short steps, highlighting the utility of this method. Computational investigations based on density functional theory clarified the chemoselectivity between the desired cyclopropanation and overoxidation process observed experimentally.
TETRAHEDRON LETTERS
(2021)
Article
Chemistry, Organic
Takahito Kuribara, Masaya Nakajima, Tetsuhiro Nemoto
Summary: The article elucidates the selectivity difference between platinum and palladium in the Friedel-Crafts-type synthesis reaction, and reveals the mechanism of the behavioral differences of the two metals through density functional theory calculations and experimental studies.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Masaya Nakajima, Yusuke Adachi, Tetsuhiro Nemoto
Summary: This study demonstrated the potential of computational simulation-based natural product syntheses as an indispensable resource in the field of organic synthesis. The authors reported the asymmetric total syntheses of several resveratrol dimers based on a comprehensive computational simulation of their biosynthetic pathways.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Masaya Nakajima, Yusuke Adachi, Tetsuhiro Nemoto
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Takahito Kuribara, Masaya Nakajima, Tetsuhiro Nemoto
Summary: Ligand design plays a crucial role in enhancing the performance of light-enabled catalytic processes. In this study, the authors synthesized a visible-light-activated secondary phosphine oxide ligand and applied it to Pd-catalyzed radical cross-coupling reactions. Through molecular design aided by computational calculations, the ligand enables ligand-to-Pd(II) and Pd(0)-to-ligand single-electron transfer under visible-light irradiation, facilitating radical cross-coupling reactions.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Dongil Choi, Noa Takahashi, Haruka Maruoka, Shingo Harada, Alina Nastke, Harald Groeger, Tetsuhiro Nemoto
Summary: We developed an enantioselective synthetic method utilizing Ir-catalyzed asymmetric hydrogenation to introduce chirality at the benzylic position, followed by Pd-catalyzed cascade cyclization for tricyclic molecular framework construction and Ag nitrene-mediated C-H amination for tetrasubstituted carbon center creation. This method provides access to a functionalized seven-membered ring-fused indole skeleton with a hydroxymethyl branch in the tetrasubstituted carbon.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Yoshinori Hashimoto, Shingo Harada, Ryosuke Kato, Kotaro Ikeda, Jannis Nonnhoff, Harald Groeger, Tetsuhiro Nemoto
Summary: This study reported a catalytic approach for the formal synthesis of more than 20 types of sarpagine/macroline alkaloids, with two key steps being the amide insertion reaction using cheap copper and biocatalytic asymmetric desymmetrization.
Article
Chemistry, Organic
Takahito Kuribara, Ayahito Kaneki, Yuma Mihara, Honoka Yuba, Tetsuhiro Nemoto
Summary: In this study, we describe a scandium-catalyzed regioselective synthesis of 5-carbonyl-4-hydroxybenzofurans via a phenol-directed intramolecular Friedel-Crafts reaction. This method was successfully applied for the total synthesis of furanoflavones. Experimental and theoretical calculations suggest that hydrogen bond interactions between the phenolic hydroxy group and the scandium complex enable regioselective intramolecular cyclization.
Article
Chemistry, Organic
Tetsuhiro Nemoto
Summary: This paper presents the advances in the synthesis of dragmacidin E, a bis-indole alkaloid isolated from a deep-water marine sponge in southern Australia. Synthetic studies conducted by the Funk, Feldman, Jia, and Nemoto groups are summarized, including the total synthesis of (±)-dragmacidin E achieved by Feldman et al. in 2011.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Physical
Yu Matsuda, Masaya Nakajima, Tetsuhiro Nemoto
Summary: Transition metal-catalyzed photoreactions have been extensively reported, but the development of ligands for these reactions is limited. This study successfully synthesized acridine-containing PNP-pincer ligands and found that the platinum complex induced photoreactions of olefins under visible light irradiation. These reactions revealed unknown reactivities of transition metals that could not be achieved with existing well-known ligands.
Article
Chemistry, Organic
Geeta Devi Yadav, Pooja Chaudhary, Balaram Pani, Surendra Singh
Summary: Chiral transition metal complexes with privileged ligands are efficient catalysts for various asymmetric organic transformations. Transition metal complexes of C1-symmetric pyrrolidine-based ligands have been widely used in asymmetric organic reactions. However, a comprehensive review article on the transition metal complexes of chiral C1-symmetric pyrrolidine-based ligands derived from (L)-proline has not been published.
TETRAHEDRON LETTERS
(2024)
